Targeting the insulin receptor: nanoparticles for drug delivery across the blood–brain barrier (BBB)
Abstract
Human serum albumin (HSA) nanoparticles (NP) were prepared by desolvation. Insulin or an anti-insulin receptor monoclonal antibody (29B4) were covalently coupled to the HSA NP, using the NHS-PEG-MAL-5000 crosslinker. Loperamide-loaded HSA NP with covalently bound insulin or the 29B4 antibodies induced significant antinociceptive effects in the tail-flick test in ICR (CD-1) mice after intravenous injection, demonstrating that insulin or these antibodies covalently coupled to HSA NP are able to transport loperamide across the blood-brain barrier (BBB) which it normally is unable to cross. Control loperamide-loaded HSA NP with immunoglobulin G antibodies yielded only marginal effects. The loperamide transport across the BBB using the NP with covalently attached insulin could be totally inhibited by the pretreatment with the antibody 29B4.
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After injection into ICR (CD-1) mice, insulin-modified HSA nanoparticles showed significant antinociceptive effects, meaning loperamide was transported across the blood-brain barrier.
“After being injected through the tails of ICR (CD-1) mice, the NP showed significant antinociceptive effects which means loperamide was able to be transported across BBB.”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [178]
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“178 They used loperamide as delivered drugs inside HSA and evaluated the potential of loperamide across the BBB. Loperamide-loaded and insulin-modi fi ed HSA presented an increase in size because of the existence of insulin agglomeration on the surface, demonstrating the successful preparation of…”
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- Authors
- Ulbrich, K., Knobloch, T., & Kreuter, J.
- Affiliations
- Goethe University Frankfurt (DE)
- Venue
- Journal of Drug Targeting
- Publisher
- Informa UK Limited
- Published
- 2010-04-13
- Volume
- 19
- Issue
- 2
- Pages
- 125-132
- ISSN
- 1026-7158 (ISSN-L)
- 1061-186X
- 1029-2330
- OpenAlex
- W2088393400
- Cited by
- 259
- References
- 2
- Citations by year
- 2026: 5 · 2025: 22 · 2024: 22 · 2023: 22 · 2022: 18 · 2021: 21 · 2020: 18 · 2019: 19 · 2018: 14 · 2017: 11 · 2016: 24 · 2015: 17 · 2014: 12 · 2013: 12 · 2012: 10
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of drug targeting (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- insulin receptor, blood-brain barrier, human serum albumin nanoparticles, loperamide, antibody conjugation, antinociception, desolvation, PEGylation, tail-flick test
- MeSH terms
- Animals, Antibodies, Monoclonal, Biological Transport, Blood-Brain Barrier, Cross-Linking Reagents, Drug Carriers, Female, Injections, Intravenous, Insulin, Loperamide, Maleimides, Mice, Inbred ICR, Polyethylene Glycols, Receptor, Insulin, Serum Albumin, Drug Delivery Systems, Mice, Nanoparticles
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